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ABSENCE OF EXCESSBODY FATNESS

VOLUME 16

This publication represents the views andexpert opinions of an IARC Working Group on

the Evaluation of Cancer-Preventive Interventions,which met in Lyon, 5–12 April 2016

LYON, FRANCE - 2018

IARC HANDBOOKS OF CANCER PREVENTION

IARC HANDBOOKS OF CANCER PREVENTION – 16

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2.2.14 Cancer of the prostate

Cancer of the prostate is the fourth most commonly diagnosed cancer worldwide, and one of the most frequent causes of cancer-related mortality in developed countries.

The relationship between body weight and prostate cancer risk is complex, for several reasons. First, prostate cancer-specific mortality (death attributed to the underlying cancer) is a proxy for incidence in some studies, whereas it is a primary end-point in other studies, along with different types of prostate cancer incidence defined by tumour characteristics. However, prostate cancer-specific mortality may be over-represented in patients who die with but not of the disease. This is a particular concern if, for example, obese patients with prostate cancer have other comorbid disease and more regular contact with the health-care system; the cancer may be more prominent in their management and may be recorded on the death certificate, even if heart disease is the underlying cause of death. Second, detection bias could also be a concern in studies of prostate cancer incidence; because obese men have lower levels of prostate-specific antigen (PSA), their tumours are more difficult to detect, and they are less likely to undergo a biopsy (Allot et al., 2013). However, potential biological mech-anisms have also been proposed to explain a lower risk of early-stage prostate cancer in men who are overweight or obese (see Section 4.3.1d).

In 2001, the Working Group of the IARC Handbook on weight control and physical activity (IARC, 2002) concluded that the evidence of an association between avoidance of weight gain and prostate cancer was inadequate. Since then, numerous prospective studies with at least 100 cases (Table 2.2.14a) and case–control studies (Table 2.2.14b) have been published, as well as several meta-analyses of observational studies addressing different measures of body fatness (Table 2.2.14c).

(a) Cohort studies

The IARC Handbook on weight control and physical activity (IARC, 2002), in the evaluation of prostate cancer risk and measures of body fatness, included 13 prospective cohort studies with at least 100 cases (not shown in Table 2.2.14a). Of those, four found a positive association and nine found no association. Notably, across all prospective studies, the highest category of BMI was overweight (25–29.9 kg/m2) but not obese (≥ 30 kg/m2).

Since 2000, associations of body fatness assessed at baseline with total prostate cancer incidence have been examined in numerous individual prospective studies with at least 100 cases and in at least two meta-analyses. In most studies, neither BMI nor weight was associated with risk (Habel et al., 2000; Schuurman et al., 2000; Lee et al., 2001; Jonsson et al., 2003; Rapp et al., 2005; Gong et al., 2006; Lukanova et al., 2006; Tande et al., 2006; Fujino et al., 2007; Giovannucci et al., 2007; Littman et al., 2007; Máchová et al., 2007; Rodriguez et al., 2007; Pischon et al., 2008; Wallström et al., 2009; Andreotti et al., 2010; Stocks et al., 2010; Bassett et al., 2012). However, in some studies statistically significant positive associations (or trends) between BMI at base-line and prostate cancer incidence were found (Engeland et al., 2003; Samanic et al., 2004, 2006; Jee et al., 2008; Barrington et al., 2015), and four prospective studies found lower risk of prostate cancer with increasing BMI (Wright et al., 2007; Bhaskaran et al., 2014; Møller et al., 2015). In a meta-analysis of 27 prospective studies, there was a statistically significant positive associ-ation with prostate cancer incidence (RR per 5 kg/m2 increase in BMI, 1.03; 95% CI, 1.00–1.07) (Renehan et al., 2008).

Associations of body fatness at baseline with stage of the disease were examined in several studies. Regarding the incidence of localized, low-grade, or non-aggressive disease, although five studies found no association (Schuurman et

Absence of excess body fatness

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al., 2000; Giovannucci et al., 2007; Pischon et al., 2008; Wallström et al., 2009; Bassett et al., 2012), at least seven other studies found an inverse asso-ciation of BMI and/or weight with the incidence of non-aggressive (Littman et al., 2007; Stocks et al., 2010), non-metastatic low- to moderate-grade (Gong et al., 2006; Rodriguez et al., 2007; Møller et al., 2016 for BMI at age 21 years), or local-ized (Wright et al., 2007; Discacciati et al., 2011; Hernandez et al., 2009 for BMI at age 21 years) prostate cancer. In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), there was evidence of a significant inverse trend between BMI and the incidence of low-grade prostate cancer in non-Hispanic White men, and a statis-tically significant positive association in African American men (Barrington et al., 2015).

Nine prospective studies found no associa-tions of BMI and/or weight with the incidence of regional or distant prostate cancer (Habel et al., 2000), advanced, high-grade, or moderately to poorly differentiated prostate cancer (Schuurman et al., 2000; Pischon et al., 2008; Discacciati et al., 2011; Møller et al., 2015), aggressive pros-tate cancer (Littman et al., 2007; Wallström et al., 2009; Stocks et al., 2010), or extraprostatic prostate cancer (Wright et al., 2007). However, five other studies found positive associations or trends of BMI and/or weight with the incidence of high-grade or advanced prostate cancer (Gong et al., 2006; Giovannucci et al., 2007; Rodriguez et al., 2007; Hernandez et al., 2009 for BMI at age 21 years; Bassett et al., 2012; Barrington et al., 2015). A meta-analysis combining data from 24 prospective studies found a statistically signifi-cant positive association between BMI and risk of advanced, high-grade, or fatal prostate cancer (RR per 5 kg/m2 increase in BMI, 1.08; 95% CI, 1.04–1.12) (WCRF/AICR, 2014).

There is considerable evidence of a positive association of BMI with prostate cancer mortality, based on findings from both individual prospec-tive studies (Rodriguez et al., 2001; Calle et al., 2003; Giovannucci et al., 2007; Wright et al.,

2007; Stocks et al., 2010 Bassett et al., 2012) and a large pooled analysis of 57 prospective studies from Europe, Japan, and the USA, reporting a relative risk of mortality per 5 kg/m2 increase in BMI of 1.13 (95% CI, 1.02–1.24) across the BMI range of 15–50 kg/m2 (Whitlock et al., 2009). However, at least six other individual prospec-tive studies found no association between BMI at baseline and death from prostate cancer (Batty et al., 2005; Fujino et al., 2007; Burton et al., 2010 for BMI at age < 30 years; Discacciati et al., 2011; Meyer et al., 2015; Møller et al., 2015). Similarly, BMI was not associated with prostate cancer mortality in a pooled analysis from the Asia Cohort Consortium (Fowke et al., 2015). [The Working Group noted that in this analysis, the reference group was men with a BMI of 22.5–24.9 kg/m2, compared with men with a BMI of 25–50 kg/m2. A possible effect of obesity (BMI > 30 kg/m2) on prostate cancer mortality might have been missed in this study.]

At least six prospective studies found no asso-ciations between BMI or weight at younger ages of adulthood and risk of prostate cancer (total, local-ized, advanced, or fatal) (Giovannucci et al., 1997; Jonsson et al., 2003; Fujino et al., 2007; Hernandez et al., 2009; Burton et al., 2010; Discacciati et al., 2011; Bassett et al., 2012), whereas in two other studies higher BMI (Schuurman et al., 2000) or weight (Littman et al., 2007) in young adulthood was significantly associated with increased total prostate cancer incidence. In the NIH-AARP cohort, both BMI and weight at age 18 years were not associated with the incidence of total prostate cancer or extraprostatic prostate cancer, whereas inverse associations with localized pros-tate cancer were reported (Ptrend = 0.04) (Wright et al., 2007). Similarly, in the Multiethnic Cohort Study and the Health Professionals Follow-up Study, BMI at age 21 years was inversely asso-ciated with the incidence of total, localized, and low- and moderate-grade prostate cancer and was not associated with the incidence of high-grade or fatal prostate cancer (Hernandez et al.,


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2009; Møller et al., 2016). Similarly, in the study by Littman et al. (2007), the positive association with weight in young adulthood (ages 18, 30, or 45 years) was restricted to the aggressive type. In a meta-analysis of nine prospective studies, Robinson et al. (2008) found a positive associ-ation between BMI in early life (i.e. < 29 years) and prostate cancer incidence or mortality (RR per 5 kg/m2 increase in BMI, 1.08).

In at least four individual prospective studies, change in neither BMI nor weight during adult-hood was associated with prostate cancer inci-dence (Jonsson et al., 2003; Samanic et al., 2006; Rodriguez et al., 2007; Rapp et al., 2008). Similarly, a meta-analysis of four prospective studies also found no associations of adult weight gain [after adjustment for age and baseline BMI or weight in all studies] with total, localized, or advanced prostate cancer incidence (Keum et al., 2015). However, in the Netherlands Cohort Study, there was suggestive evidence of an inverse trend between increase in BMI from age 20 years to baseline (≥ 6 kg/m2) and total prostate cancer incidence (Ptrend = 0.07), and this associa-tion was statistically significant for poorly differ-entiated or undifferentiated prostate tumours (Schuurman et al., 2000). In the Vitamins and Lifestyle (VITAL) cohort, both weight loss and weight gain were associated with a lower risk of non-aggressive prostate cancer, but there was no association with aggressive prostate cancer (Littman et al., 2007). In the NIH-AARP cohort, weight gain from age 18 years to baseline was not associated with prostate cancer incidence (total, localized, or extraprostatic), but was associated with prostate cancer mortality (Ptrend = 0.009) (Wright et al., 2007).

The association between waist circumfer-ence and total prostate cancer incidence was examined in at least eight individual prospective studies, and no study found evidence of statisti-cally significant associations with total prostate cancer incidence (Giovannucci et al., 1997; Lee et al., 2001; MacInnis et al., 2003; Gong et al.,

2006; Tande et al., 2006; Pischon et al., 2008; Wallström et al., 2009; Møller et al., 2015). On the basis of four prospective studies, the WCRF Continuous Update Project summary (WCRF/AICR, 2014) found no dose–response association between waist circumference and risk of total or non-advanced prostate cancer, but a statisti-cally significant positive association with risk of advanced or fatal prostate cancer (RR per 10 cm increase, 1.12; 95% CI, 1.04–1.21).

(b) Case–control studies

Case–control studies of BMI and other adiposity indices in relation to prostate cancer risk are presented in Table 2.2.14b. In the IARC Handbook on weight control and physical activity (IARC, 2002), 15 case–control studies of BMI and prostate cancer were reviewed (not shown here). Since then, at least 35 case–control studies and 5 meta-analyses including case–control study designs, focused on the association between weight, BMI, or waist circumference and pros-tate cancer, have been conducted in Asia (China, India, Japan, and Pakistan), the Caribbean (Barbados and Jamaica), Europe, the Islamic Republic of Iran, Nigeria, North America, and Oceania (Australia and New Zealand). In all of these studies, BMI was assessed on the basis of self-reported height and body weight, or body weight and height verified at the time of a hospital consultation.

Positive associations between high BMI and total prostate cancer incidence were reported in six of the case–control studies. Bashir et al. (2014), in a hospital-based case–control study in Pakistan with 140 cases and 280 controls, found a significant increase in the risk of prostate cancer for men with BMI > 25 kg/m2 (OR, 5.78; 95% CI, 2.67–12.6). In a multicentre hospital-based case–control study in Italy, Dal Maso et al. (2004) iden-tified a dose–response relationship between BMI at age 30 years and prostate cancer risk, based on 1257 cases (Ptrend = 0.004). Ganesh et al. (2011) reported a 2-fold greater risk of prostate cancer


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in Indian men with BMI ≥ 25 kg/m2 (OR, 2.1; 95% CI, 1.1–4.4). A hospital-based case–control study in France found a positive association between BMI > 29 kg/m2 and risk of prostate cancer (OR, 2.47; 95% CI, 1.41–4.34) (Irani et al., 2003). Similarly, a study in Canada reported a signif-icant 27% increase in risk of prostate cancer in men with BMI ≥ 30 kg/m2 compared with those with BMI < 25 kg/m2 (Pan et al., 2004).

An inverse association between BMI and prostate cancer has also been reported in several studies. Beebe-Dimmer et al. (2009), in a hospital-based case–control study in the USA, found an inverse relationship between high BMI (≥ 30 kg/m2) and prostate cancer risk in Caucasian men, based on 494 cases (OR, 0.51; 95% CI, 0.33–0.80), but not in African American men. Similarly, a study in Canada found a statis-tically significant inverse relationship between BMI ≥ 30 kg/m2 and prostate cancer risk (OR, 0.72; 95% CI, 0.60–0.87), but no associations with waist circumference or waist-to-hip ratio were found (Boehm et al., 2015). A population-based case–control study in the Islamic Republic of Iran (Hosseini et al., 2010), with 137 cases and 137 controls, also found a significant inverse relation-ship between high BMI (≥ 25 kg/m2) and prostate cancer risk (OR, 0.4; 95% CI, 0.2–0.8). Finally, Agalliu et al. (2015) conducted a small hospi-tal-based case–control study in Nigeria, with 50 cases and 50 controls. Inverse associations were reported for weight (OR per kg increase, 0.97; 95% CI, 0.94–1.00) and waist circumference (OR per cm increase, 0.91; 95% CI, 0.87–0.96).

One additional case–control study found an increased risk of total prostate cancer in men with an increased waist circumference (Beebe-Dimmer et al., 2007).

Three meta-analyses that included case–control studies suggested a small increase in risk of prostate cancer associated with higher BMI (Bergström et al., 2001; MacInnis & English, 2006; Robinson et al., 2008). In one additional meta-analysis, a significant positive association

with adult weight was observed for high-risk (RR, 1.13; 95% CI, 1.00–1.28) and fatal (RR, 1.58; 95% CI, 1.01–2.47) prostate cancer subtypes (Chen et al., 2016).

Six case–control studies differentiated pros-tate cancer by grade, stage, or aggressiveness, and generally reported positive associations of BMI, waist circumference, or waist-to-hip ratio with prostate cancers with higher Gleason scores. Fowke et al. (2012) analysed 809 hospital-based cases and 1057 controls in the USA by Gleason score. On the basis of 135 cases, BMI and waist circumference were marginally associated with increased risk of high-grade prostate cancer (OR per 1 kg/m2 increase in BMI, 1.04; 95% CI, 1.00–1.08 and OR per 1 cm increase in waist circumference, 1.01; 95% CI, 0.99–1.03). Jackson et al. (2010) separated patients with high-grade prostate cancer in their hospital-based case–control study (243 cases and 275 controls) in Jamaica. Waist circumference and waist-to-hip ratio were positively associated with high-grade prostate cancer after adjustment for BMI. A dose–response relationship was also observed for waist circumference, and no association was found with BMI. A case–control study in Italy observed significant positive associations of BMI and prostate cancer of Gleason score 7–10 only (Ptrend < 0.01) (Dal Maso et al., 2004). Liu et al. (2005) conducted a population-based sibling case–control study in the USA with 439 cases and 479 controls and found no association of aggres-sive prostate cancer (defined as Gleason score ≥ 7 or tumour stage T2C or greater) with increased BMI, whereas an inverse association was observed for lean body mass (Ptrend = 0.02). Nemesure et al. (2012) conducted a population-based case–control study in Barbados with 963 cases and 941 controls and reported a positive association of waist circumference with all prostate cancers (OR for highest versus lowest quartiles, 1.84; 95% CI, 1.19–2.85), which did not hold when strati-fying by disease grade. Robinson et al. (2005) in the USA reported an inverse association between


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BMI > 30 kg/m2 at age 20–29 years and advanced prostate cancer [based on 12 cases].

Several studies assessed BMI and body weight at different ages, and BMI/weight change. In a population-based case–control study in Sweden, Gerdtsson et al. (2015) investigated several anthropometric measures, including BMI and weight, at multiple time points in life. Weight increase in adolescence (age 16–22 years) was associated with increased risk of prostate cancer (OR per 5 kg increase in weight, 1.05; 95% CI, 1.01–1.09), and increase in BMI and weight in middle age (age 44–50 years) was associated with increased mortality from prostate cancer, and with increased metastasis. Weight gain of 10.0–14.9 kg in adulthood was significantly associated with a 3–4-fold greater risk of pros-tate cancer in a population-based case–control study in Japan (Mori et al., 2011). In the same study, BMI of 23.0–24.9 kg/m2 at age 20 years was associated with a reduced risk of prostate cancer (OR, 0.47; 95% CI, 0.22–0.98) (Mori et al., 2011) [based on 11 cases only]. In contrast, a total of 16 case–control studies conducted in Australia, Canada, the Czech Republic, Italy, Japan, New Zealand, Spain, Sweden, Switzerland, the United Kingdom, and the USA reported no associations between risk of total prostate cancer and BMI or other adiposity indices at different ages (Putnam et al., 2000; Sharpe & Siemiatycki, 2001; Giles et al., 2003; Friedenreich et al., 2004; Porter & Stanford, 2005; Robinson et al., 2005; Wuermli et al., 2005; Cox et al., 2006; Gallus et al., 2007; Máchová et al., 2007; Nagata et al., 2007; Magura et al., 2008; Dimitropoulou et al., 2011; Pelucchi et al., 2011; Möller et al., 2013; Alvarez-Cubero et al., 2015; Zhang et al., 2015) or BMI change or weight gain from early adulthood (Putnam et al., 2000; Giles et al., 2003; Friedenreich et al., 2004).

(c) Mendelian randomization studies

Three Mendelian randomization studies have been conducted in this context (Table 2.2.14d).

Lewis et al. (2010) showed that each additional A allele of the FTO rs9939609 SNP was associ-ated with an increase of 0.56 kg/m2 (P = 0.007) in BMI across all groups (cases and controls). Estimates obtained from Mendelian random-ization analyses provided odds ratios of 0.77 (95% CI, 0.52–1.15; P = 0.20) for prostate cancer and 1.35 (95% CI, 0.90–2.03; P = 0.14) for high-grade versus low-grade cancer with each 1 kg/m2 increase in BMI.

Davies et al. (2015) extended this work by using a genetic risk score based on 32 SNPs associated with BMI (Speliotes et al., 2010) as an instrument for BMI within a much larger sample size. Each increase of 1 standard devia-tion in genetically predicted BMI was associated on average with a nonsignificant 2% reduction in risk (95% CI, 0.96–1.00; P = 0.07) in any prostate cancer diagnosis.

In Mendelian randomization analyses that used genetic risk scores based on 77 SNPs for adult BMI (Locke et al., 2015) and 15 SNPs for childhood BMI (Felix et al., 2016), Gao et al. (2016) found no strong evidence for associations of childhood or adult BMI with either total or aggressive prostate cancer risk.

[Although results from Lewis et al. (2010) and Davies et al. (2015) point towards an inverse association between BMI and prostate cancer risk, this association was not significant and was not consistently found in all three studies.]


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Table 2.2.14a Cohort studies of measures of body fatness and cancer of the prostate

Reference Cohort Location Follow-up period

Total number of subjects Incidence/mortality

Organ site or cancer subtype (ICD code)

Exposure categories

Exposed cases

Relative risk (95% CI)

Covariates Comments

Giovannucci et al. (1997) Health Professionals Follow-up Study USA 1986–1994

47 781 Incidence

Prostate, advanced

BMI at age 21 yr < 20 20–21.9 22–22.9 23–23.9 24–25.9 ≥ 26 [Ptrend]

81

117 59 56 60 26

1.00 0.91 (0.69–1.22) 0.88 (0.62–1.24) 0.77 (0.54–1.10) 0.71 (0.50–1.02) 0.53 (0.33–0.86) [< 0.006]

Age, height

Prostate, all BMI at age 21 yr < 20 20–21.9 22–22.9 23–23.9 24–25.9 ≥ 26 [Ptrend]

229 353 188 200 223 104

1.00 0.98 (0.83–1.16) 1.00 (0.82–1.22) 1.03 (0.84–1.26) 1.00 (0.82–1.22) 0.87 (0.67–1.12) [0.60]

WC also not associated with increased risk

Habel et al. (2000) Kaiser Permanente USA 1964–1973 to 1996

70 712 Incidence

Prostate BMI < 22.7 22.7–24.3 24.4–25.9 26–27.9 > 27.9

2079 total 1.00 1.09 (0.93–1.27) 1.04 (0.89–1.21) 1.04 (0.90–1.21) 0.99 (0.85–1.15)

Age, race, year of birth Weight also not associated with increased risk No associations were observed in results stratified by race

Prostate, regional/distant

BMI < 22.7 22.7–24.3 24.4–25.9 26–27.9 > 27.9

578 total 1.00 0.84 (0.62–1.13) 1.05 (0.80–1.39) 1.04 (0.79–1.37) 0.91 (0.69–1.20)

Schuurman et al. (2000) Netherlands Cohort Study The Netherlands 1986–1982

58 279 Incidence

Prostate BMI at baseline < 22 22–23 24–25 26–27 ≥ 28 [Ptrend] per 2 kg/m2

63

164 236 150

62

1.00 1.20 (0.84–1.73) 1.35 (0.95–1.90) 1.26 (0.87–1.83) 0.89 (0.58–1.37) [0.73] 1.00 (0.92–1.07)

Age, family history of prostate cancer, SES; BMI change results also adjusted for BMI at age 20 yr

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Exposure categories

Exposed cases


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Schuurman et al. (2000) (cont.)

58 279 Incidence

BMI at age 20 yr < 19 19–20.9 21–22.9 23–24.9 ≥ 25 [Ptrend] per 2 kg/m2

57

122 176 119 44

1.00 1.06 (0.72–1.56) 1.09 (0.76–1.58) 1.39 (0.93–2.06) 1.33 (0.81–2.19) [0.02] 1.08 (0.99–1.18)

BMI change −9.2 to < 0 0–1.9 2–3.9 4–5.9 6–7.9 ≥ 8 [Ptrend] per 2 kg/m2

47

120 176 113 43 19

1.19 (0.74–1.90) 1.00 1.32 (0.98–1.79) 1.04 (0.74–1.47) 0.83 (0.52–1.31) 0.67 (0.36–1.23) [0.07] 0.93 (0.84–1.03)

Prostate, localized TNM: T0–2, M0

BMI, per 2 kg/m2 239 totalBMI at baseline 0.96 (0.86–1.06)BMI at age 20 yr 1.18 (1.04–1.35)BMI change 0.87 (0.74–1.02)

Prostate, advanced TNM: T3–4, M0; T0–4, M1


Table 2.2.14a (continued)


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Exposure categories

Exposed cases


Covariates Comments

Schuurman et al. (2000) (cont.)

Prostate, well-differentiated


Prostate, moderately differentiated


Prostate, poorly differentiated or undifferentiated


Lee et al. (2001) Harvard Alumni Health Study USA 1988–1993

8922 Incidence

Prostate BMI at baseline < 22.5 22.5–24.9 25.0–27.4 27.5 [Ptrend]

87

172 134

46

1.00 1.27 (0.94–1.71) 1.26 (0.92–1.72) 1.02 (0.68–1.53) [0.71]

Age, smoking, alcohol consumption, paternal history of prostate cancer

WC also not associated with increased risk BMI at age 18 yr (available for 92% of the men) also not associated with increased risk

Rodriguez et al. (2001) Cancer Prevention Study I (CPS I) USA 1959–1972

381 638 Mortality

Prostate ICD-7: 177

BMI < 25 25–29.99 ≥ 30 [Ptrend]

782 698 110

1.00 1.02 (0.92–1.14) 1.27 (1.04–1.56) [0.06]

Age, race, height, education level, exercise, smoking status, family history of prostate cancer

Calle et al. (2003) Cancer Prevention Study II (CPS II) USA 1982–1998

404 576 Mortality

Prostate BMI 18.5–24.9 25–29.9 30–34.9 ≥ 35 [Ptrend]

1681 1971

311 41

1.00 1.08 (1.01–1.15) 1.20 (1.06–1.36) 1.34 (0.98–1.83) [< 0.001]

Age, education level, smoking, physical activity, alcohol consumption, marital status, race, aspirin use, fat consumption, vegetable consumption


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Exposure categories

Exposed cases


Covariates Comments

Engeland et al. (2003) Norwegian clinical population Norway 1963–1999 to 2001

951 466 Incidence

Prostate ICD-7: 177

BMI < 18.5 18.5–24.9 25–29.9 ≥ 30 [Ptrend]

147

16 720 14 524

1923

0.92 (0.78–1.08) 1.00 1.07 (1.05–1.09) 1.09 (1.04–1.15) [0.001]

Age at BMI measurement, birth cohort

In stratified analyses by age at BMI measurement, no differences in risk by age strata were observed

Jonsson et al. (2003) Swedish Twin Registry Sweden 1969–2003

8998 Incidence

Prostate ICD-7: 177

BMI at baseline < 18.5 18.5–24.9 25.0–29.9 ≥ 30

6

355 248

22

1.4 (0.6–3.1) 1.0 1.0 (0.8–1.2) 1.0 (0.6–1.5)

Age; BMI at age 25 yr and 40 yr also controlled for BMI at baseline

No associations were observed in stratified analyses by age at diagnosis (≥ 70 yr vs < 70 yr)

BMI at age 25 yr < 18.5 18.5–24.9 ≥ 25

4

436 64

0.5 (0.2–1.5) 1.0 1.0 (0.7–1.3)

BMI at age 40 yr < 18.5 18.5–24.9 25.0–29.9 ≥ 30

6

368 155

13

2.5 (1.1–5.5) 1.0 0.9 (0.7–1.1) 0.9 (0.5–1.6)

Adult weight change (kg)< 0 0–5 6–10 11–20 ≥ 21

96 178 114 95 21

0.9 (0.7–1.2) 1.0 1.0 (0.8–1.3) 0.9 (0.7–1.2) 1.1 (0.8–1.8)

Samanic et al. (2004) United States Veterans cohort USA 1969–1996

4 500 700 Incidence

Prostate ICD-9: 185

Obesity Age, calendar year Obesity defined as discharge diagnosis of obesity: ICD-8: 277; ICD-9: 278.0

Non-obese Obese

Black men: 15 272

815

1.00 1.12 (1.04–1.20)

Non-obese Obese

White men: 45 901

3206

1.00 1.19 (1.15–1.24)



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Exposure categories

Exposed cases


Covariates Comments

Batty et al. (2005) Whitehall Study United Kingdom 1967–2002

18 403 Mortality

Prostate BMI 18.5–24.9 25.0–29.9 ≥ 30 [Ptrend]

243 175 13

1.00 0.92 (0.75–1.13) 0.91 (0.51–1.63) [0.45]

Age, employment grade, physical activity, smoking, marital status, prevalent disease, past-year weight loss, BP medication, height, skinfold thickness, systolic BP, plasma cholesterol, glucose intolerance, diabetes

Rapp et al. (2005) Vorarlberg VHM&PP Austria 1985–2001

67 447 Incidence

Prostate ICD-9: 185

BMI 18.5–24.9 25–29.9 30–34.9 ≥ 35 [Ptrend]

446 583

99 10

1.00 1.03 (0.91–1.17) 0.82 (0.66–1.03) 0.73 (0.39–1.37) [0.16]

Age, smoking status, occupation

Gong et al. (2006) Prostate Cancer Prevention Trial (PCPT) USA N/A–2003

10 258 Incidence

Prostate BMI < 25 25–26.9 27–29.9 ≥ 30 [Ptrend]

1936 total 1.00 0.91 (0.79–1.05) 0.96 (0.83–1.10) 0.96 (0.83–1.10) [0.67]

Age, race, treatment, diabetes, family history of prostate cancer

Analyses of the association of WC with total prostate, and low-grade and high-grade subtypes also reported

Prostate, low-grade

BMI < 25 25–26.9 27–29.9 ≥ 30 [Ptrend]

1300 total 1.00 0.88 (0.74–1.04) 0.88 (0.75–1.04) 0.82 (0.69–0.98) [0.03]

Prostate, high-grade

BMI < 25 25–26.9 27–29.9 ≥ 30 [Ptrend]

521 total 1.00 0.97 (0.75–1.27) 1.09 (0.85–1.40) 1.29 (1.01–1.67) [0.04]


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Exposure categories

Exposed cases


Covariates Comments

Lukanova et al. (2006) Northern Sweden Health and Disease Cohort (NSHDC) 1985–2003

33 424 Incidence/mortality

Prostate BMI 18.5–23.4 23.5–25.3 25.4–27.6 ≥ 27.1 [Ptrend]

93

114 129 125

1.00 1.00 (0.76–1.32) 0.96 (0.74–1.26) 0.89 (0.68–1.16) [0.31]

Age, calendar year, smoking

Samanic et al. (2006) Swedish Construction Worker Cohort Sweden 1958–1999

362 552 Incidence

Prostate ICD-7: 177

BMI 18.5–24.9 25–29.9 ≥ 30 [Ptrend]

3003 3160 528

1.00 1.06 (1.01–1.12) 1.09 (0.99–1.19) [< 0.05]

Attained age, calendar year, smoking

107 815 (in BMI change analysis) Incidence

6-yr BMI change −4% to 4.9% 5–9.9% 10–14.9% ≥ 15% [Ptrend]

1281

417 97 22

1.00 1.09 (0.98–1.22) 0.93 (0.75–1.14) 0.75 (0.49–1.15) [> 0.5]

Tande et al. (2006) Atherosclerosis Risk in Communities (ARIC) Study USA 1987–2000

6332 Incidence

Prostate BMI < 24.7 24.7–26.9 27.0–29.7 ≥ 29.8

94 99 91

101

1.00 1.17 (0.88–1.55) 0.97 (0.72–1.29) 1.14 (0.86–1.50)

Age, race WC also not associated with increased risk Men with metabolic syndrome were 27% less likely to develop prostate cancer

Fujino et al. (2007) Japan Collaborative Cohort Study for Evaluation of Cancer (JACC) Japan NR

NR Mortality

Prostate BMI < 18.5 18.5–24 25–29 ≥ 30

17

107 31 1

1.39 (0.83–2.34) 1.00 1.56 (1.04–2.34) 0.87 (0.12–6.29)

Age, area of study [No information reported on follow-up period or total number of participants included in the study] Weight at baseline and at age 20 yr also not associated with increased mortality



347




Exposure categories

Exposed cases


Covariates Comments

Giovannucci et al. (2007) Health Professionals Follow-up Study USA 1986–2002 Updated follow-up from Giovannucci et al. (1997)

47 750 Incidence

Prostate BMI < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30 [Ptrend]

3544 total 1.00 1.21 1.36 1.24 1.24 1.13 (0.91–1.41) [0.84]

Age, time period, BMI at age 21 yr, height, pack-years of smoking, physical activity, family history of prostate cancer, diabetes, race, energy intake, intake of processed meat, fish, α-linolenic acid, tomato sauce, vitamin E supplements

[CI provided only for the last BMI category] No association was observed with BMI for low-grade or high-grade prostate cancer (based on Gleason score)

Prostate, advanced TNM: T3b or T4 or N1 or M1

BMI < 21 ≥ 30 [Ptrend]

523 total 1.00 1.34 (0.79–2.26) [≤ 0.05]

47 750 Mortality

Prostate BMI 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30

323 total 1.00 1.44 1.30 1.43 1.80 (1.10–2.93)

Littman et al. (2007) Vitamins and Lifestyle (VITAL) cohort USA 2000–2004

34 754 Incidence

Prostate BMI at baseline < 25 25–29.9 ≥ 30 [Ptrend]

218 435 155

1.0 1.1 (0.97–1.4) 0.87 (0.71–1.1) [0.13]

Age, family history of prostate cancer, race, baseline BMI, recent PSA screening

BMI at ages 18 yr, 30 yr, and 45 yr also not associated with increased risk

Prostate, non-aggressive Gleason score < 7

BMI at baseline < 25 25–29.9 ≥ 30 [Ptrend]

129 222

73

1.0 0.99 (0.79–1.2) 0.69 (0.52–0.93) [0.01]


Prostate, aggressive Gleason score 7–10

BMI at baseline < 25 25–29.9 ≥ 30 [Ptrend]

85

209 179

1.0 1.4 (1.1–1.8) 1.1 (0.83–1.6) [0.69]



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Exposure categories

Exposed cases


Covariates Comments

Littman et al. (2007) (cont.)

34 754 Incidence

Prostate Weight (lb) at age 18 yr Age, family history of prostate cancer, race, baseline BMI, recent PSA screening

For non-aggressive prostate cancer, weight at age 18 yr and 30 yr was not associated with an increased risk

< 139 139–154 155–170 ≥ 171 [Ptrend]

166 203 198 231

1.0 1.2 (0.96–1.5) 1.1 (0.93–1.4) 1.2 (1.0–1.5) [0.08]

Weight (lb) at age 30 yr< 154 154–169 170–184 ≥ 185 [Ptrend]

174 192 188 241

1.0 1.2 (0.95–1.4) 1.1 (0.93–1.4) 1.3 (1.0–1.6) [0.03]


194 182 224 200

1.0 1.0 (0.82–1.2) 1.1 (0.91–1.3) 1.1 (0.87–1.3) [0.46]

Weight (lb) at baseline< 173 174–189 190–214 ≥ 215 [Ptrend]

211 181 233 192

1.0 1.0 (0.83–1.2) 0.99 (0.82–1.2) 0.92 (0.75–1.1) [0.35]

Prostate, non-aggressive Gleason score < 7

Weight (lb) at baseline Weight gain of ≥ 30 lb since age 18 yr associated with 33% lower risk of incidence

< 173 174–189 190–214 ≥ 215 [Ptrend]

130 90

116 92

1.00 0.82 (0.62–1.1) 0.81 (0.63–1.1) 0.71 (0.54–0.93) [0.02]

Prostate, aggressive Gleason score 7–10

Weight (lb) at age 18 yr Age, family history of prostate cancer, race, baseline BMI, recent PSA screening

< 139 139–154 155–170 ≥ 171 [Ptrend]

71 94 89

117

1.00 1.3 (0.92–1.7) 1.2 (0.86–1.6) 1.4 (1.0–1.9) [0.04]



349




Exposure categories

Exposed cases


Covariates Comments

Littman et al. (2007) (cont.)

34 754 Incidence


72 84 93

119

1.0 1.2 (0.90–1.7) 1.4 (0.99–1.9) 1.5 (1.1–2.0) [0.01]


72 86

111 102

1.0 1.3 (0.93–1.8) 1.5 (1.1–2.0) 1.4 (1.1–2.0) [0.032]

Weight (lb) at baseline Weight gain since age 18 yr not associated with risk of incidence

< 173 174–189 190–214 ≥ 215 [Ptrend]

78 87

115 98

1.0 1.3 (0.96–1.8) 1.3 (0.97–1.7) 1.3 (0.93–1.7) [0.23]

Máchová et al. (2007) National Cancer Registry Nested case–control study in the population of the Šumperk District Czech Republic 1987–2002

17 334 Incidence

Prostate ICD-10: C61

BMI 18.5–24.9 25–29.9 ≥ 30

338 total 1.00 1.05 (0.72–1.39) 0.97 (0.66–1.41)

Age, smoking, hypertension, height


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Exposure categories

Exposed cases


Covariates Comments

Rodriguez et al. (2007) Cancer Prevention Study II (CPS II) Nutrition Cohort USA 1992–2003

69 991 Incidence

Prostate BMI < 25 25–27.4 27.5–29.9 30–34.9 ≥ 35 [Ptrend]

1935 1742 920 556

99

1.00 1.02 (0.96–1.09) 0.98 (0.90–1.06) 0.94 (0.85–1.04) 0.91 (0.75–1.12) [0.14]

Age, race, education level, family history of prostate cancer, energy intake, smoking status, PSA testing, diabetes, physical activity; Weight change also adjusted for BMI in 1982 and height

Weight change (lb), 1982–1992 When stratifying by subtype, weight change also not associated with increased risk for any subtype

≥ 21 loss 11–20 loss 6−19 loss 5 loss to 5 gain 6–10 gain 11–20 gain ≥ 21 gain

113 349 541

2450 751 687 322

0.84 (0.69–1.02) 0.84 (0.75–0.95) 0.98 (0.89–1.08) 1.00 0.98 (0.90–1.06) 0.97 (0.89–1.05) 0.89 (0.79–1.00)

Prostate, non-metastatic, low-grade TNM: T1–3, N0, M0 Gleason score ≤ 8

BMI < 25 25–27.4 27.5–29.9 30–34.9 ≥ 35 [Ptrend]

1544 1409

700 412

73

1.00 1.03 (0.96–1.10) 0.92 (0.84–1.01) 0.86 (0.77–0.97) 0.84 (0.66–1.06) [0.002]

Prostate, non-metastatic high-grade TNM: T1–3, N0, M0 Gleason score > 8

BMI < 25 25–27.4 27.5–29.9 ≥ 30 [Ptrend]

239 180 140 103

1.00 0.87 (0.72–1.06) 1.23 (1.00–1.53) 1.22 (0.96–1.55) [0.03]

69 991 Incidence or mortality

Prostate, metastatic or fatal TNM: T4, Nx, Mx or Tx, N1–2, Mx or Tx, Nx, M1

BMI < 25 25–27.4 27.5–29.9 ≥ 30 [Ptrend]

92

104 46 46

1.00 1.41 (1.06–1.87) 1.14 (0.79–1.63) 1.54 (1.06–2.23) [0.05]



351




Exposure categories

Exposed cases


Covariates Comments

Wright et al. (2007) NIH-AARP cohort USA 1995–2000

172 961 Incidence

Prostate ICD-9: 185 ICD-10: C61

BMI < 25 25–29.9 30–34.9 35–39.9 ≥ 40 [Ptrend]

3076 5054 1532 269

55

1.00 1.00 (0.95–1.04) 0.97 (0.91–1.03) 0.84 (0.74–0.95) 0.65 (0.50–0.85) [0.0008]

Age, race, smoking status, education level, diabetes, family history of prostate cancer For BMI at age 18 yr, also BMI at baseline, height

BMI at age 18 yr < 18.5 18.5–20.9 21–22.9 23–24.9 ≥ 25 [Ptrend]

723

1787 1510 775 641

0.95 (0.87–1.04) 1.00 1.01 (0.95–1.09) 0.90 (0.83–0.98) 0.93 (0.84–1.02) [0.17]

Weight (kg) at age 18 yr, quintiles Age, race, smoking status, education level, diabetes, family history of prostate cancer, BMI, height

< 58.6 58.7–64.5 64.6–69.9 70–76.7 > 76.7 [Ptrend]

1004 1338 1043 1138 1071

1.0 1.01 (0.93–1.10) 0.99 (0.91–1.09) 0.99 (0.91–1.09) 0.92 (0.84–1.02) [0.08]

Weight (kg) at baseline, quintiles Weight at baseline also not associated with increased risk for localized and with metastatic prostate cancer subtypes

< 74.5 74.6–81.3 81.4–87.2 87.3–97.2 > 97.2 [Ptrend]

1126 1224 1204 1157 1014

1.0 1.02 (0.93–1.11) 1.01 (0.92–1.10) 1.00 (0.91–1.09) 0.91 (0.82–1.00) [0.99]


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Exposure categories

Exposed cases


Covariates Comments

Wright et al. (2007) (cont.)

172 961 Incidence

Weight change (kg), age 18 yr to baseline Weight change also not associated with increased risk for localized and for extraprostatic prostate cancer subtypes

< −4 −4 to 3.9 4–9.9 10–19.9 20–29.9 30–39.9 ≥ 40 [Ptrend]

161 430 936

1896 1425 469 277

1.00 (0.83–1.19) 1.0 1.04 (0.93–1.17) 1.12 (1.00–1.24) 1.12 (1.00–1.26) 0.99 (0.87–1.14) 1.03 (0.88–1.20) [0.81]

Prostate, localized TNM: T1a to T2b, N0, M0

BMI < 25 25–29.9 30–34.9 35–39.9 ≥ 40 [Ptrend]

2652 4328 1277

236 48

1.00 0.99 (0.94–1.04) 0.94 (0.88–1.01) 0.86 (0.75–0.98) 0.67 (0.50–0.89) [0.0006]



633

1570 1317 653 535

0.95 (0.86–1.04) 1.0 1.01 (0.94–1.09) 0.87 (0.80–0.96) 0.89 (0.80–0.99) [0.04]


< 58.6 58.7–64.5 64.6–69.9 70–76.7 > 76.7 [Ptrend]

881 1185 903 988 891

0.95 (0.86–1.04) 1.00 1.01 (0.94–1.09) 0.87 (0.80–0.96) 0.89 (0.80–0.99) [0.04]

Prostate, extraprostatic TNM: T3 or T4, N1, or M1

BMI < 25 25–29.9 30–34.9 ≥ 35 [Ptrend]

424 726 255 40

1.0 1.03 (0.91–1.16) 1.14 (0.97–1.33) 0.68 (0.49–0.94) [0.64]

Age, race, smoking status, education level, diabetes, family history of prostate cancer For BMI at age 18 yr, also BMI, height



353




Exposure categories

Exposed cases


Covariates Comments

Wright et al. (2007) (cont.)

172 961 Incidence


90

217 193 122 106

0.98 (0.77–1.26) 1.00 1.04 (0.86–1.27) 1.11 (0.88–1.39) 1.15 (0.90–1.47) [0.18]


< 58.6 58.7–64.5 64.6–69.9 70–76.7 > 76.7 [Ptrend]

123 153 140 150 180

1.0 0.95 (0.74–1.20) 1.08 (0.84–1.38) 1.03 (0.80–1.33) 1.18 (0.91–1.54) [0.13]

Wright et al. (2007) NIH-AARP cohort USA 1995–2000

Mortality Prostate ICD-9: 185 ICD-10: C61

BMI < 25 25–29.9 30–34.9 ≥ 35 [Ptrend]

44 87 31 11

1.0 1.25 (0.87–1.80) 1.46 (0.92–2.33) 2.12 (1.08–4.15) [0.02]


Weight at baseline also associated with increased risk


13 18 25 16 11

1.67 (0.82–3.42) 1.0 1.65 (0.90–3.02) 1.71 (0.86–3.39) 1.35 (0.62–2.95) [0.73]

Weight (kg) at age 18 yr also not associated with increased mortality

Weight change (kg), age 18 yr to baseline Age, race, smoking status, education level, diabetes, family history of prostate cancer, BMI, height

< −4 −4 to 3.9 4–9.9 10–19.9 20–29.9 30–39.9 40 [Ptrend]

3 6

12 23 24 10 8

1.18 (0.29–4.74) 1.0 1.06 (0.40–2.83) 1.17 (0.47–2.92) 1.74 (0.69–4.40) 2.05 (0.72–5.90) 2.98 (0.99–9.04) [0.009]


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Exposure categories

Exposed cases


Covariates Comments

Jee et al. (2008) National Health Insurance Corporation (NHIC) medical evaluation Republic of Korea 1992–2006

770 556 Incidence

Prostate BMI < 20.0 20.0–22.9 23.0–24.9 25.0–29.9 ≥ 30.0 [Ptrend]

265 896 747 638

23

0.67 (0.56–0.80) 0.87 (0.77–0.98) 1.00 0.95 (0.83–1.08) 1.39 (0.90–2.17) [< 0.0001]

Age, smoking

Pischon et al. (2008) EPIC cohort 8 European countries, 1992–2000 (8.5 yr follow-up on average)

129 502 Incidence


BMI, quintiles < 23.6 23.6–25.3 25.4–27 27.1–29.3 ≥ 29.4 [Ptrend] per 5 kg/m2

2446 total 1.00 1.06 (0.93–1.20) 1.08 (0.95–1.23) 0.95 (0.83–1.09) 0.99 (0.86–1.13) [0.37] 0.96 (0.90–1.02)

Study centre, age, smoking status, education level, alcohol consumption, physical activity, height

Also examined hip circumference and waist-to-hip ratio WC also not associated with increased risk

Prostate, localized TNM: T0–T2 and N0/Nx, M0

BMI, quintiles < 23.6 23.6–25.3 25.4–27 27.1–29.3 ≥ 29.4 [Ptrend] continuous

991 total 1.00 1.09 (0.89–1.34) 1.02 (0.83–1.25) 0.88 (0.71–1.10) 0.95 (0.77–1.18) [0.22] 0.92 (0.84–1.01)



Prostate, advanced TNM: T3–T4 and/or N1–N3 and/or M1

BMI < 23.6 23.6–25.3 25.4–27 27.1–29.3 ≥ 29.4 [Ptrend] continuous

499 total 1.00 1.05 (0.78–1.40) 1.25 (0.94–1.66) 1.08 (0.81–1.46) 1.17 (0.86–1.58) [0.34] 1.09 (0.96–1.24)





355




Exposure categories

Exposed cases


Covariates Comments

Pischon et al. (2008) (cont.)

129 502 Incidence

Prostate, low-grade Gleason score < 7


841 total 1.00 0.97 (0.78–1.21) 0.95 (0.77–1.19) 0.83 (0.66–1.04) 0.84 (0.66–1.06) [0.06] 0.88 (0.79–0.98)



Prostate, high-grade Gleason score ≥ 7


580 total 1.00 1.26 (0.96–1.65) 1.34 (1.02–1.76) 1.16 (0.87–1.54) 1.23 (0.92–1.65) [0.37] 1.04 (0.92–1.18)



Rapp et al. (2008) VHM&PP Austria 1985–2002

28 711 Incidence


BMI change, annual Age, smoking status, blood glucose, occupational group, BMI at baseline

< −0.1 −0.1– < 0.1 0.1– < 0.3 0.3– < 0.5 ≥ 0.5 [Ptrend]

164 317 231 72 12

0.96 (0.79–1.16) 1.00 1.00 (0.85–1.19) 1.01 (0.78–1.31) 0.43 (0.24–0.76) [0.06]

Hernandez et al. (2009) Multiethnic Cohort USA 1993/1996–2002/2005

83 879 Incidence

Prostate, advanced

BMI at age 21 yr No associations were observed with high grade either Inverse associations were observed with localized and with low-grade subtypes

< 18.5 18.5–24.9 ≥ 25.0 [Ptrend]

41 475 86

0.96 (0.69–1.35) 1.00 1.09 (0.85–1.40) [0.46]


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Exposure categories

Exposed cases


Covariates Comments

Wallström et al. (2009) Malmö Diet and Cancer Study Sweden 1991–2005

11 063 Incidence

Prostate ICD-9: 185

BMI < 18.5 18.5–24.9 25–29.9 ≥ 30 [Ptrend]

8

287 417 105

2.29 (1.13–4.63) 1.00 1.02 (0.88–1.19) 1.06 (0.84–1.33) [0.15]

Age, height, cohabitation status, SES, alcohol consumption, smoking, prevalent diabetes, physical activity, country of birth, total intake of eicosapentaenoic acid, docosahexaenoic acid, red meat, calcium


Prostate, aggressive TNM: T3–T4, or N1 or M1, or Gleason score ≥ 8, or PSA > 50 ng/mL

BMI < 18.5 18.5–24.9 25–29.9 ≥ 30 [Ptrend]

4

102 140

35

3.15 (1.15–8.62) 1.00 0.99 (0.76–1.29) 1.02 (0.69–1.52) [0.16]


Prostate, non-aggressive Not stage T3–T4, or N1 or M1, or Gleason score ≥ 8, or PSA > 50 ng/mL

BMI < 18.5 18.5–24.9 25–29.9 ≥ 30 [Ptrend]

4

183 274 69

0.84 (0.63–1.11) 1.00 1.16 (0.89–1.50) 1.11 (0.85–1.44) [0.65]


Whitlock et al. (2009) Prospective Studies Collaboration (pooled analysis of 57 cohorts from Europe, Japan, and the USA) Follow-up varied by cohort

894 576 Mortality

Prostate ICD-9: 185

BMI, per 5 kg/m2 For BMI 15–25 For BMI 25–50 For BMI 15–50

578 665

1.00 (0.75–1.32) 1.09 (0.91–1.31) 1.13 (1.02–1.24)

Study, sex, age, smoking



357




Exposure categories

Exposed cases


Covariates Comments

Andreotti et al. (2010) Agricultural Health Study USA 1993–2005

39 628 Incidence

Prostate BMI < 18.5 18.5–24.9 25–29.9 30–34.9 ≥ 35 [Ptrend]

0

308 696 226

44

– 1.00 1.06 (0.89–1.27) 0.89 (0.71–1.13) 0.94 (0.61–1.44) [0.56]

Race, smoking status, exercise, family history of prostate cancer

Burton et al. (2010) Glasgow Alumni Cohort United Kingdom 1948–1968 to 2009

9549 Incidence


BMI, young adult (age < 30 yr) Smoking, SES, height< 19 19–22.9 23–24.9 ≥ 25 per 1 kg/m2 [Ptrend]

25 125

33 14

1.30 (0.84–1.99) 1.00 1.14 (0.78–1.68) 1.18 (0.68–2.06) 1.00 (0.93–1.06) [0.89]

9549 Mortality


BMI, young adult (age < 30 yr)< 19 19–22.9 23–24.9 ≥ 25 per 1 kg/m2 [Ptrend]

14 59 21 8

1.58 (0.88–2.83) 1.00 1.52 (0.92–2.50) 1.43 (0.68–3.00) 1.02 (0.93–1.11) [0.74]

Stocks et al. (2010) Swedish Construction Worker Cohort Sweden 1971–2004

336 159 Mortality

Prostate ICD-7: 177

BMI < 21.9 21.9– < 23.5 23.5– < 25 25– < 27 ≥ 27 [Ptrend]

230 383 476 702 810

1.00 1.17 (1.00–1.39) 1.09 (0.93–1.27) 1.26 (1.08–1.46) 1.28 (1.11–1.49) [0.0004]

Birth cohort, smoking No association of BMI with incidence of prostate (total), or aggressive prostate cancer subtypes. Significant negative association observed between BMI and incidence for non-aggressive prostate cancer subtype


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358




Exposure categories

Exposed cases


Covariates Comments

Discacciati et al. (2011) Sweden 1998–2008

36 959 Incidence

Prostate, localized TNM: T1–2 and NX–0 and MX–0 or PSA < 20 ng/mL or Gleason score < 7

BMI at baseline < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30

62

245 401 467 204 124

0.78 (0.54–1.13) 1.00 1.00 (0.94–1.06) 0.95 (0.86–1.05) 0.88 (0.76–1.02) 0.71 (0.53–0.94)

BMI at age 30 yr, age, energy intake, physical activity, education level, smoking, family history of prostate cancer, diabetes

BMI at age 30 yr < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30 per 5 kg/m2

287 539 467 154

41 15

1.01 (0.91–1.12) 1.00 0.99 (0.94–1.05) 0.99 (0.89–1.10) 0.98 (0.82–1.16) 0.96 (0.69–1.34) 0.98 (0.87–1.12)

Prostate, advanced TNM: T3–4 and NX–1 and MX–1 or PSA > 100 ng/mL or Gleason score > 7

BMI at baseline < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30 per 5 kg/m2

27 72

163 150

79 47

0.97 (0.85–1.10) 1.00 1.02 (0.95–1.08) 1.03 (0.90–1.18) 1.05 (0.85–1.31) 1.11 (0.73–1.68) 1.04 (0.88–1.22)


BMI at age 30 yr < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30 per 5 kg/m2

108 185 164

69 8 4

1.09 (0.92–1.29) 1.00 0.96 (0.88–1.04) 0.91 (0.77–1.09) 0.87 (0.65–1.15) 0.76 (0.44–1.30) 0.90 (0.73–1.11)



359




Exposure categories

Exposed cases


Covariates Comments

Discacciati et al. (2011) (cont.)

36 959 Mortality

Prostate BMI at baseline < 21 21–22.9 23–24.9 25–27.4 27.5–29.9 ≥ 30 per 5 kg/m2

11 35 62 59 29 23

0.91 (0.75–1.11) 1.00 1.05 (0.95–1.16) 1.11 (0.89–1.36) 1.16 (0.83–1.63) 1.34 (0.70–2.55) 1.12 (0.87–1.43)


BMI at age 30 yr also not associated with increased risk

Bassett et al. (2012) Melbourne Collaborative Cohort Study (MCCS) Australia 1990–2004 Same cohort as MacInnis et al. (2003)

16 525 Incidence


BMI at baseline < 18.5 18.5–22.9 23–24.9 ≥ 25 per 5 kg/m2 [Ptrend]

111 259 757 247

0.73 (0.59–0.91) 1.00 0.98 (0.85–1.12) 0.96 (0.80–1.15) 1.06 (0.97–1.17) [0.19]

Country of birth, education level

No associations were observed between weight at baseline, BMI or weight (kg) at age 18 yr, or WC, and prostate cancer risk (incidence)

Prostate, non-aggressive Not Gleason score > 7, stage 4, or death from prostate cancer


83

194 527 160

0.73 (0.56–0.94) 1.00 0.91 (0.77–1.08) 0.83 (0.67–1.03) 0.99 (0.89–1.10) [0.83]


No associations were observed between weight at baseline, BMI or weight (kg) at age 18 yr, or WC, and non-aggressive prostate cancer risk (incidence)

Prostate, aggressive Gleason score > 7, stage 4, or death from prostate cancer


28 65

230 87

0.74 (0.47–1.15) 1.00 1.17 (0.89–1.54) 1.33 (0.96–1.84) 1.27 (1.08–1.49) [0.004]


No associations were observed between weight at baseline, BMI or weight (kg) at age 18 yr, or WC, and aggressive prostate cancer risk (incidence)

16 525 Mortality



7

23 71 38

0.53 (0.23–1.24) 1.00 0.95 (0.59–1.53) 1.52 (0.89–2.58) 1.49 (1.11–2.00) [0.01]


Weight at baseline also associated with increased mortality No association was observed with BMI or weight at age 18 yr and mortality


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Exposure categories

Exposed cases


Covariates Comments

Bhaskaran et al. (2014) Clinical Practice Research Datalink United Kingdom 1987–2012

2 379 320 Incidence


BMI per 5 kg/m2 [Ptrend]

24 901 total 0.98 (0.95–1.00) [0.0042]

Age, diabetes, smoking, alcohol consumption, SES, calendar year, sex

No differences were found in non-smokers only

Barrington et al. (2015) Participants in the Selenium and Vitamin E cancer Prevention Trial (SELECT) USA 2001–2008

26 035 Incidence

Prostate BMI Non-Hispanic White: Age, education level, diabetes, smoking, family history of prostate cancer, study arm

For African Americans, BMI < 25.0 in Non-Hispanic Whites was taken as reference

< 25.0 25.0–27.5 27.5–29.9 30–34.9 35–50 [Ptrend]

289 438 333 299

94

1.00 1.12 (0.97–1.30) 1.04 (0.89–1.22) 0.96 (0.82–1.13) 0.94 (0.74–1.19) [0.63]

BMI African American:< 25.0 25.0–27.5 27.5–29.9 30–34.9 35–50 [Ptrend]

39 63 57 74 37

1.28 (0.91–1.80) 1.67 (1.27–2.21) 1.64 (1.23–2.19) 1.68 (1.29–2.18) 1.90 (1.34–2.70) [0.03]

26 035 Incidence

Prostate, low-grade Gleason score 2–6

BMI Non-Hispanic White: Age, education level, diabetes, smoking, family history of prostate cancer, study arm

< 25.0 25.0–27.5 27.5–29.9 30–34.9 35–50 [Ptrend]

182 293 202 170

51

1.00 1.18 (0.98–1.42) 1.00 (0.82–1.22) 0.86 (0.70–1.06) 0.80 (0.58–1.09) [0.02]


16 37 35 37 23

0.80 (0.48–1.43) 1.47 (1.03–2.10) 1.52 (1.05–2.20) 1.27 (0.83–1.82) 1.77 (1.14–2.76) [0.05]



361




Exposure categories

Exposed cases


Covariates Comments

Barrington et al. (2015) (cont.)

26 035 Incidence

Prostate, high-grade Gleason score 7–10

BMI Non-Hispanic White: Age, education level, diabetes, smoking, family history of prostate cancer, study arm

< 25.0 25.0–27.5 27.5–29.9 30–34.9 35–50 [Ptrend]

84 115 101 104

37

1.00 1.03 (0.78–1.37) 1.11 (0.83–1.49) 1.18 (0.88–1.58) 1.33 (0.90–1.97) [0.01]


11 19 17 29 12

1.32 (0.70–2.51) 1.94 (1.17–3.22) 1.87 (1.10–3.16) 2.53 (1.64–3.90) 2.39 (1.29–4.43) [0.02]

Fowke et al. (2015) Pooled analysis in Asia Cohort Consortium (ACC) Different Asian countries (1963–2001) to 2006

522 736 Mortality

Prostate BMI 12–19.9 20–22.4 22.5–24.9 25–50 [Ptrend]

142 188 184 120

0.98 (0.78–1.23) 0.92 (0.75–1.13) 1.00 1.08 (0.85–1.36) [0.58]

Age, education level, population density, marital status, history of severe cancer, heart disease, or stroke at baseline

Similar results were observed in stratified analyses by region

Meyer et al. (2015) Population-based Swiss cohort study Switzerland 1977–2008

35 703 in cohort, number of men NR Mortality


BMI < 25 25–29.9 ≥ 30

170 total 1.00 1.45 (1.03–2.04) 1.54 (0.93–2.55)

Age, survey, alcohol consumption, physical activity, civil status, years of education, nationality, diet

Those who were overweight and who also smoked (ever smoking) had a higher risk


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Covariates Comments

Møller et al. (2015) Diet, Cancer and Health Study Denmark 1993–2011

26 044 Incidence

Prostate BMI 15.4–24.9 25–29.9 30–52.7 [Ptrend]

649 920 244

1.00 0.94 (0.85–1.04) 0.86 (0.74–0.99) [0.03]

NR WC showed no association with total prostate cancer incidence Inverse associations were observed with the upper quartile of body fat percentage (15% decreased risk)

Prostate Stage 3–4

BMI 15.4–24.9 25–29.9 30–52.7 [Ptrend]

208 314 104

1.00 1.00 (0.84–1.19) 1.14 (0.90–1.44) [0.37]

NR WC also no associated with advanced prostate cancer incidence Positive associations were observed with the upper quartile of body fat percentage (31% increased risk)

26 044 Mortality

Prostate BMI 15.4–24.9 25–29.9 30–52.7 [Ptrend]

92

147 51

1.00 1.10 (0.85–1.43) 1.27 (0.90–1.80) [0.19]

Stage at diagnosis WC also not associated with increased mortality A positive association was observed with increasing body fat percentage

Møller et al. (2016) Health Professionals Follow-up Study USA 1986–2010

47 491 Incidence and mortality

Prostate BMI at age 21 yr < 20 20–21.9 22–23.9 24–25.9 ≥ 26 [Ptrend] per 5 kg/m2

825

1546 1852 1132 588

0.99 (0.90–1.08) 1.00 0.98 (0.91–1.05) 0.92 (0.85–1.00) 0.89 (0.80–0.98) [0.01] 0.94 (0.89–0.98)

Age, calendar time, ethnicity, physical activity, energy intake, smoking, diabetes, family history of prostate cancer, PSA testing

When analysing cumulative BMI average, the significant decrease in risk persisted only in those younger than 65 yr



363




Exposure categories

Exposed cases


Covariates Comments

Møller et al. (2016) (cont.)

47 491 Incidence and mortality

Prostate, fatal BMI at age 21 yr < 20 20–21.9 22–23.9 24–25.9 ≥ 26 [Ptrend] per 5 kg/m2

94

181 177 88 51

0.83 (0.64–1.07) 1.00 0.92 (0.74–1.14) 0.74 (0.57–0.97) 0.77 (0.56–1.07) [0.20] 0.88 (0.75–1.02)

BMI at age 21 yr also not associated with lethal subtypes (incident cases and deaths due to prostate cancer or distant metastases at diagnosis or during follow-up)

Prostate, high-grade Gleason score 8–10


85

181 204 130

79

0.82 (0.63–1.07) 1.00 0.93 (0.75–1.15) 0.91 (0.72–1.16) 1.10 (0.83–1.45) [0.27] 1.03 (0.90–1.19)

Prostate, moderate-grade Gleason score 7


233 446 548 333 159

0.98 (0.83–1.15) 1.00 0.98 (0.86–1.11) 0.90 (0.78–1.04) 0.77 (0.64–0.93) [0.01] 0.87 (0.80–0.95)

Age, calendar time, ethnicity, physical activity, energy intake, smoking, diabetes, family history of prostate cancer, PSA testing

Prostate, low-grade Gleason score 2–6


333 620 735 465 236

1.01 (0.88–1.16) 1.00 0.94 (0.84–1.05) 0.90 (0.79–1.02) 0.88 (0.75–1.03) [0.03] 0.93 (0.87–1.01)

BMI, body mass index (in kg/m2); BP, blood pressure; CI, confidence interval; EPIC, European Prospective Investigation into Cancer and Nutrition; ICD, International Classification of Diseases; N/A, not applicable; NIH-AARP, National Institutes of Health–AARP Diet and Health Study; NR, not reported; PSA, prostate-specific antigen; SD, standard deviation; SES, socioeconomic status; TNM, tumour–node–metastasis; VHM&PP, Vorarlberg Health Monitoring and Prevention Program; WC, waist circumference; yr, year or years


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364 Table 2.2.14b Case–control studies of measures of body fatness and cancer of the prostate

Reference Study location Period

Total number of cases Source of controls

Exposure categories Exposed cases Relative risk (95% CI)

Adjustment for confounding

Comments

Putnam et al. (2000) USA 1986–1989

101 Population

BMI < 24.1 24.1–26.6 > 26.6

27 31 38

1.0 1.0 (0.6–1.7) 1.3 (0.8- 2.2)

Age

BMI change (%) from age 20 yr> 5% loss 5% loss to 5% gain 5.1–10.0% gain 10.1–15.0% gain > 15.0% gain

1 12 15 14 51

0.2 (0.02–1.5) 1.0 1.3 (0.6–2.7) 1.0 (0.5–1.9) 1.3 (0.8–2.2)

Weight (kg) < 74.8 74.8–83.9 > 83.9

22 41 33

1.0 1.4 (0.8–2.3) 1.2 (0.7–2.1)

Sharpe & Siemiatycki (2001) Canada 1979–1985

399 Population

BMI < 24.05 24.05–26.66 > 26.66

127 128 141

0.87 (0.6–1.22) 1.00 1.14 (0.81–1.61)

Age, ethnicity, respondent status, family income, alcohol consumption

Giles et al. (2003) Australia 1994–1998

1476 Population

BMI at age 21 yr < 20.5 20.5–22.1 22.2–23.9 > 23.9

353 372 337 332

1.00 0.99 (0.79–1.23) 0.96 (0.76–1.20) 1.10 (0.88–1.39)

Age, country of birth, family history of prostate cancer, study centre, calendar year

No associations were observed for weight or WC at age 21 yr

Irani et al. (2003) France 1993–1999

194 Hospital

BMI < 29 > 29

NR 1.00 2.47 (1.41–4.34)

Age


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Comments

Dal Maso et al. (2004) Italy 1991–2002

1294 Hospital

BMI at baseline < 24.22 24.22–26.18 26.18–28.41 ≥ 28.41 [Ptrend]

301 346 324 319

1.00 1.18 (0.95–1.47) 1.12 (0.89–1.40) 1.18 (0.94–1.47) [0.23]

Age, study centre, education level, physical activity, family history of prostate cancer

No associations were observed between weight (kg), waist-to-hip ratio, or lean body mass and prostate cancer. When stratified by grade, associations of BMI at diagnosis were only significant with prostate cancer of Gleason score 7–10 (384 cases, Ptrend < 0.01)

BMI at age 30 yr < 22.65 22.65–24.69 ≥ 24.69 [Ptrend]

406 437 414

1.00 1.33 (1.09–1.62) 1.22 (1.01–1.48) [0.004]

Friedenreich et al. (2004) Canada 1997–2000

988 Population

BMI, quartiles Q1 Q2 Q3 Q4 [Ptrend]

252 236 245 254

1.00 0.95 (0.74–1.23) 0.98 (0.76–1.26) 1.07 (0.83–1.38) [0.57]

Age, region, education level, average lifetime total alcohol intake, first-degree family history of prostate cancer, number of times had PSA test done, number of digital rectal exams, total lifetime physical activity

Weight, quartiles Q1 Q2 Q3 Q4 [Ptrend]

268 233 262 224

1.00 0.93 (0.72–1.21) 1.00 (0.78–1.28) 0.91 (0.70–1.18) [0.18]

Weight gain (kg) since age 20 yr< 4.54 4.54–13.6 13.6–20.4 ≥ 20.4 [Ptrend]

241 286 238 215

1.00 1.14 (0.89–1.47) 1.05 (0.82–1.36) 0.91 (0.70–1.19) [0.26]

Table 2.2.14b (continued)

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Comments

Pan et al. (2004) Canada 1994–1997

1801 Population

BMI < 25 25–30 ≥ 30 [Ptrend]

1.00 1.16 (0.94–1.43) 1.27 (1.09–1.47) [0.026]

Age group, province of residence, education level, pack-years of smoking, alcohol consumption, total energy intake, vegetable intake, dietary fibre intake, recreational physical activity

Liu et al. (2005) USA NR

439 Population (sibling-based)

BMI, quartiles Q1 Q2 Q3 Q4 [Ptrend]

106 112 110 106

1.00 1.57 (0.85–2.89) 1.43 (0.78–2.61) 0.91 (0.49–1.70) [0.73]

Age, education, calorie intake

Results are presented for high-aggressiveness prostate cancer (Gleason score ≥ 7, or tumour stage T2C or greater)

LBM, quartiles Q1 Q2 Q3 Q4 [Ptrend]

LBM > 66.3: 113 104 114 103

1.00 0.58 (0.31–1.08) 0.43 (0.22–0.81) 0.41 (0.20–0.84) [0.02]

Porter & Stanford (2005) USA 1993–1996

753 Population

BMI 18–24.4 24.4–26.5 26.5–29.1 29.1–55 [Ptrend]

195 202 178 178

1.00 1.04 (0.78–1.39) 0.85 (0.64–1.14) 0.91 (0.66–1.21) [0.04]

Age, race, education level, smoking, family history of prostate cancer, prostate cancer screening, dietary fat, energy intake

Weight (kg) < 77.2 77.2–85.8 85.9–95.3 > 95.3 [Ptrend]

175 222 193 163

1.00 0.96 (0.70–1.30) 0.77 (0.56–1.06) 0.74 (0.53–1.03) [0.03]

Robinson et al. (2005) USA 1997–2000

568 Population

BMI at age 20–29 yr < 25.0 25.0–29.9 ≥ 30.0

361 191 12

1.00 1.13 (0.87–1.47) 0.40 (0.20–0.81)

Age, race, family history of prostate cancer, saturated fat intake

This study evaluated the association with advanced prostate cancer



367





Comments

Wuermli et al. (2005) Switzerland 1997–2002

504 Hospital

BMI < 30 > 30

NR 1.00 0.97 (0.93–1.01)

Age, BMI, diabetes, lipid-lowering drugs

Cox et al. (2006) New Zealand 1996–1998

550 Population

BMI 5 yr before interview, quintiles Age No associations were observed between BMI or weight at age 20 yr and prostate cancer

Q1 Q2 Q3 Q4 Q5

50 40

105 122 233

1.0 0.9 (0.5–1.6) 0.8 (0.6–1.2) 0.9 (0.6–1.3) 0.9 (0.6–1.3)

Beebe-Dimmer et al. (2007) USA 1996–2002

139 Population (community-based)

WC (cm) ≤ 102 > 102

59 1.00 1.84 (1.17–2.91)

Age, smoking history

Gallus et al. (2007) Italy 1991–2002

219 Hospital

BMI < 24.84 24.84–27.76 ≥ 27.77 [Ptrend]

69 80 70

1.0 1.3 (0.8–2.0) 1.2 (0.8–1.9) [0.38]

Age, education level, study centre, occupational physical activity, family history of prostate cancer

Máchová et al. (2007) Czech Republic 1987–2002

338 Population

BMI 18.5–< 25 25–30 ≥ 30

NR 1.00 1.05 (0.72–1.39) 0.97 (0.66–1.41)

Age, smoking, hypertension, height

Nagata et al. (2007) Japan 1996–2003

200 Hospital

BMI 1 yr before diagnosis Smoking BMI at age 40–45 yr not associated with increased risk of prostate cancer

< 23.0 23.0–24.9 > 25.0 [Ptrend]

81 60 59

1.00 1.28 (0.87–1.87) 1.06 (0.72–1.55) [0.65]

Magura et al. (2008) USA 2004–2006

312 Hospital

BMI < 25 ≥ 25

30

282

1.00 1.04 (0.58–1.85)

Age, family history of prostate cancer, type 2 diabetes, smoking, use of multivitamins, use of statins


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Comments

Beebe-Dimmer et al. (2009) USA 2001–2004

637 Hospital

BMI < 30 ≥ 30

–

208

1.00 0.51 (0.33–0.80)

Age, PSA screening history, hypertension, diabetes, low HDL, high triglycerides

Inverse association was observed only in Caucasians (n = 494). No association observed in African Americans (n = 381)

Hosseini et al. (2010) Islamic Republic of Iran 2005–2008

137 Population

BMI ≤ 25 > 25

105

35

1.0 0.4 (0.2–0.8)

Age, family history of prostate cancer, history of other cancers, history of prostatitis, alcohol consumption, smoking, physical activity

[Discrepancy in the number of reported cases]

Jackson et al. (2010) Jamaica 2005–2007

243 Hospital

BMI, quartiles Q4 vs Q1 (ref) [Ptrend]

NR 0.90 (0.42–1.91) [0.28]

BMI: age, education level, medical history, first-degree family history of prostate cancer, smoking, physical activity WC and waist-to-hip ratio: age, height and BMI as continuous; education level, current smoker, physical activity

Results are presented for high-grade cancer (Gleason score ≥ 7) 12% of the cases were obese

WC, tertiles T3 vs T1 (ref) [Ptrend]

5.57 (1.43–18.63) [0.008]

Waist-to-hip ratio < 0.95 ≥ 0.95

1.00 2.94 (1.34–6.38)

Dimitropoulou et al. (2011) United Kingdom 2001–2008

960 Population

BMI < 25.0 25.0–29.9 > 30.0 [Ptrend]

264 481 174

1.00 0.98 (0.82–1.16) 0.83 (0.67–1.03) [0.097]

Age, family history of prostate cancer

WC, tertiles T1 T2 T3 [Ptrend]

385 286 289

1.00 1.01 (0.85–1.20) 0.94 (0.80–1.12) [0.517]

Ganesh et al. (2011) India 1999–2001

123 Hospital

BMI < 25 ≥ 25

41 76

1.0 2.1 (1.1–4.4)

Age, religion, education level, hypertension



369





Comments

Mori et al. (2011) Japan 2007–2008

117 Population

BMI < 21.0 21.0–22.9 23.0–24.9 ≥ 25.0 [Ptrend]

14 29 41 33

1.00 1.05 (0.50–2.21) 1.63 (0.77–3.45) 1.39 (0.66–2.96) [0.07]

Dietary intake, physical activity, smoking, alcohol consumption

BMI of 23–25 at age 20 yr associated with a 53% reduced risk (based on 11 cases) No associations between body weight at age 20 yr and prostate cancer riskWeight (kg)

< 55 55.0–64.9 65.0–74.9 ≥ 75.0

7

52 45 13

1.00 1.49 (0.57–3.85) 1.74 (0.65–4.64) 1.64 (0.55–4.91)

Weight gain (kg) in adult life< 5 5.0–9.9 10.0–14.9 ≥ 15

18 24 43 32

1.00 1.22 (0.58–2.55) 3.55 (1.71–7.39) 1.73 (0.83–3.59)

Pelucchi et al. (2011) Italy 1991–2002

1294 Hospital

BMI < 28 ≥ 28

909 381

1.00 0.98 (0.83–1.17)

Age, study centre, education level, smoking, alcohol consumption, physical activity, family history of prostate cancer, non-alcohol energy intake

WC (cm) < 94 ≥ 94

242 730

1.00 1.13 (0.91–1.40)

Abdominal obesity (combined WC, BMI)No Yes

470 820

1.00 1.02 (0.86–1.21)

Fowke et al. (2012) USA NR

809 Hospital

BMI per 1 kg/m2 increase

135

1.04 (1.00–1.08)

Age, PSA, prostate volume, race, family history of prostate cancer, current treatment for diabetes, benign prostatic hyperplasia, CVD, or hyperlipidaemia

Results are presented for high-grade (Gleason score 8–10) prostate cancer

WC per 1 cm increase

135

1.01 (0.99–1.03)


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Comments

Nemesure et al. (2012) Barbados 2002–2011

963 Population

WC (cm), quartiles Q1: < 84 Q2: 84–92 Q3: 92–99 Q4: ≥ 99

NR 1.00 1.36 (1.01–1.85) 1.67 (1.14–2.44) 1.84 (1.19–2.85)

Age, marital status, religion, occupation, smoking, family history of prostate cancer, BMI

Study in African Barbadian population. When stratifying by high-grade (n = 434) vs low-grade (n = 480) prostate cancer, the associations were not significant in either group

Möller et al. (2013) Sweden 2001–2002

1499 Population

BMI < 22.5 22.5– < 25 25– < 27.5 ≥ 27.5 per 5 kg/m2 [Ptrend]

382 655 295 120

1.00 0.94 (0.76–1.15) 0.90 (0.71–1.15) 0.96 (0.69–1.33) 0.98 (0.83–1.16) [0.54]

Age, region of residence, time span between first and last recalled weight

No associations with BMI when stratifying by low- and intermediate-grade vs high-grade prostate cancer No significant associations with BMI at age 20 yr

Bashir et al. (2014) Pakistan 2012–2013

140 Hospital

BMI ≤ 25 > 25

66 74

1.00 5.78 (2.67–12.6)

Age, lifestyle (physical activity), family history of prostate cancer, smoking, diet

Agalliu et al. (2015) Nigeria 2011–2012

50 Hospital

BMI < 25 25–29.9 ≥ 30

21 21 8

1 1.39 (0.59–3.28) 1.35 (0.42–4.36)

Age

Weight (kg) per kg increase

0.97 (0.94–1.00)

WC (cm) per cm increase

0.91 (0.87–0.96)

Alvarez-Cubero et al. (2015) Spain 2011–2014

100 Hospital

BMI ≥ 30 vs < 30

31 1.65 (0.36–7.57)

Age, residential area, family history of prostate cancer



371





Comments

Boehm et al. (2015) Canada 2005–2012

1933 Population

BMI < 25 25–29.9 ≥ 30

649 922 351

1.00 0.87 (0.74–1.01) 0.72 (0.60–0.87)

Age, ancestry, first-degree family history of prostate cancer, annual physician visits, number of PSA tests within 5 yr before index date

No associations were observed with waist-to-hip ratio

WC (cm) < 102 ≥ 102

1073

711

1.00 1.03 (0.89–1.19)

Gerdtsson et al. (2015) Sweden 1974–1996

1355 Population

Weight at age 16–22 yr per 5 kg increase

Incidence: 1.05 (1.01–1.09)

No associations were observed with BMI or weight at age 44–50 yr and prostate cancer risk BMI and weight at age 44–50 yr also associated with metastasis

BMI at age 44–50 yr per 5 kg increase

Mortality: 1.08 (1.03–1.13)

Weight at age 44–50 yr per 5 kg increase

Mortality: 1.11 (1.03–1.19)

Zhang et al. (2015) China 2013–2014

101 Hospital

BMI < 24 ≥ 24

35 66

1.00 2.51 (0.18–9.52)

WC, BP, triglyceride levels, free blood glucose

BMI, body mass index (in kg/m2); BP, blood pressure; CI, confidence interval; CVD, cardiovascular disease; HDL, high-density lipoprotein; LBM, lean body mass; NR, not reported; PSA, prostate-specific antigen; SD, standard deviation; WC, waist circumference; yr, years or years


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372 Table 2.2.14c Meta-analyses of measures of body fatness and cancer of the prostate

Reference Total number of studies Total number of cases

Organ site or cancer subtype

Exposure categories



Comments

Bergström et al. (2001)

6 observational studies (4 cohort and 2 case–control) 4592

Prostate BMI per 1 kg/m2 increase

1.01 (1.00–1.02)

Different adjustment by study, some non-adjusted

MacInnis & English (2006)

43 observational studies (22 cohort and 21 case–control) (9 studies for WC) 68 753


1.05 (1.01–1.08)

Different adjustment by study

No associations were found with WC

Renehan et al. (2008) 27 prospective studies 70 421


1.03 (1.00–1.07)

Between-study heterogeneity of I2 = 73% No differences in the results were observed by region (Asia-Pacific, Australia, Europe, North America)

Robinson et al. (2008)

9 cohort studies and 7 case–control studies NR

Prostate BMI before age 29 yr, per 5 kg/m2 increase

Cohort: 1.08 (0.97–1.19) Case–control: 1.07 (0.98–1.17)

Age for all; other factors depending on the study

Guh et al. (2009) 7 cohort studies NR

Prostate BMI Normal Overweight Obesity

1.00 1.14 (1.00–1.31) 1.05 (0.85–1.30)

NR

Esposito et al. (2013) 13 observational studies (cohort and case–control) 4634

Prostate BMI High vs low

1.05 (0.97–1.15)

NR [Cut-off values differ by study]

WCRF/AICR (2014) Continuous Update Project

24 prospective studies for BMI, 4 for WC 11 149

Prostate, advanced BMI per 5 kg/m2 increase

1.08 (1.04–1.12)

NR Advanced prostate cancer includes advanced, high-grade, and fatal prostate cancers


1.12 (1.04–1.21)


373

Reference Total number of studies Total number of cases

Organ site or cancer subtype

Exposure categories



Comments

Keum et al. (2015) 4 prospective studies 6882

Prostate Weight gain per 5 kg increase

0.98 (0.94–1.02)

Age and baseline BMI or weight in all, and different additional covariates depending on the study

Prostate, localized Weight gain per 5 kg increase

0.96 (0.92–1.00)

Prostate, advanced Weight gain per 5 kg increase

1.04 (0.99–1.09)


1.03 (0.99–1.07)

Chen et al. (2016) 9 observational studies (5 cohort, 1 nested case–control, and 3 case–control) 22 338

All Low- and intermediate-grade High-grade Fatal

Adult weight per 5 kg increase

1.01 (0.94–1.08) 0.97 (0.87–1.07) 1.13 (1.00–1.28) 1.58 (1.01–2.47)

Age (in all studies except one) and different covariates depending on the study

BMI, body mass index (in kg/m2); CI, confidence interval; NR, not reported; WC, waist circumference; WCRF/AICR, World Cancer Research Fund/American Institute for Cancer Research; yr, years or years

Table 2.2.14c (continued)

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374 Table 2.2.14d Mendelian randomization studies of measures of body fatness and cancer of the prostate

Reference Study

Characteristics of study population

Sample size Exposure (unit) Odds ratio (95% CI) and P value (with each unit increase in exposure) of the association between the exposure and outcome(s)


Lewis et al. (2010) Prostate Testing for Cancer and Treatment Study (ProtecT)

Men aged 50–69 yr from 300 general practices across 9 regions in the United Kingdom

4540 (1550 cases and 2990 controls)

BMI per 1 kg/m2 increase

All: 0.77 (0.52–1.15) P = 0.20

Age, centre

per 1 kg/m2 increase

High-grade vs low-grade: 1.35 (0.90–2.03) P = 0.15

Davies et al. (2015) Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) Consortium

19 independent studies of individuals of European descent

41 062 (20 848 cases and 20 214 controls)

Increase of 1 SD in genetically predicted BMI

0.98 (0.96–1.00) P = 0.07

8 principal components of population stratification

Gao et al. (2016) Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium

6 studies of individuals of European ancestry

26 884 (14 160 cases and 12 724 controls)

Increase of 1 SD in genetically predicted BMI (~0.073 kg/m2) N/AChildhood BMI: All:

1.01 (0.83–1.22) P = 0.91Aggressive: 1.10 (0.83–1.45) P = 0.49

Adult BMI: All: 1.00 (0.96–1.04) P = 0.97Aggressive: 1.02 (0.96–1.08) P = 0.44

BMI, body mass index (in kg/m2); CI, confidence interval; N/A, not applicable; SD, standard deviation; vs, versus; yr, years or years


375

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